The overall objectives of this research proposal are to investigate the roles of gastrointestinal (GI) hormones in the digestive processes. We have available specific radioimmunoassays (RIAs) for gastrin, secretin, cholecystokinin (CCK), glucagon, and pancreatic poly peptide (PP). We have, in different stages of development, RIAs for bombesin, motilin, growth hormone, vasocactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP) and somatostatin. We will continue our studies to validate these assay systems. These RIAs will be used to study the temporal pattern or release of GI hormones after various stimuli. We continue to study the relationship between the pituitary hormone and adrenal hormones on the release of GI hormones in normal rats and dogs. We will determine if there are different molecular forms of CCK, secretin, VIP, PP and GIP in plasma and tissue of man, dog and cats. The pattern of release and tissue levels of different molecular forms of the hormones will be studied in animals, normal man and patients with duodenal ulcer disease, before and after operation. We will attempt to identify a negative feedback mechanism for the release of CCK. We will continue to study the influences of disease on the pattern of release of GI hormones: specifically, gastrin in Zollinger-Ellison syndrome and secretin in normal man and duodenal ulcer patients. We will correlate biologic activity of GI hormones with measurements of their circulating concentrations, as measured by RIA. We plan to continue to study the mechanisms (organ and cellular) by which GI hormones are catabolized. We will study the synthesis of GI hormones in cell cultures by incorporation of labeled amino acids into hormones and by RIA of culture media. We will continue to develop the monoclonal antibodies which produce specific GI hormones. We will continue to study the possible trophic effects of GI hormones on tumors growing in hampsters and rats. We will investigate the binding of different hormones to target tissue with emphasis upon development of receptor-type assays for GI hormones. We will determine the storage pattern of individual GI hormones in segments of GI mucosa and the ability of different agents to stimulate or inhibit the release of GI hormones from segments of the gut.